Genetic Variant MTCH2:c.87+882T>C (chr11-47641497-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014342.4(MTCH2):c.87+882T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,066 control chromosomes in the GnomAD database, including 7,004 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 7004 hom., cov: 32)

Consequence

MTCH2
NM_014342.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.179

Publications

185 publications found

Variant links:

Genes affected

MTCH2 (HGNC:17587): (mitochondrial carrier 2) This gene encodes a member of the SLC25 family of nuclear-encoded transporters that are localized in the inner mitochondrial membrane. Members of this superfamily are involved in many metabolic pathways and cell functions. Genome-wide association studies in human have identified single-nucleotide polymorphisms in several loci associated with obesity. This gene is one such locus, which is highly expressed in white adipose tissue and adipocytes, and thought to play a regulatory role in adipocyte differentiation and biology. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study showed this gene to be an authentic stop codon readthrough target that can produce two isoforms from the same mRNA by use of alternative in-frame translation termination codons. [provided by RefSeq, Dec 2017]

MTCH2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_014342.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014342.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTCH2	NM_014342.4	MANE Select	c.87+882T>C	intron	N/A	NP_055157.1	Q9Y6C9
MTCH2	NM_001317231.2		c.87+882T>C	intron	N/A	NP_001304160.1
MTCH2	NM_001317232.2		c.87+882T>C	intron	N/A	NP_001304161.1	E9PIE4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTCH2	ENST00000302503.8	TSL:1 MANE Select	c.87+882T>C	intron	N/A	ENSP00000303222.3	Q9Y6C9
MTCH2	ENST00000947886.1		c.87+882T>C	intron	N/A	ENSP00000617945.1
MTCH2	ENST00000864071.1		c.87+882T>C	intron	N/A	ENSP00000534130.1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42562

AN:

151946

Hom.:

6992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0928

Gnomad AMI

AF:

0.637

Gnomad AMR

AF:

0.366

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.280

AC:

42586

AN:

152066

Hom.:

7004

Cov.:

AF XY:

0.281

AC XY:

20915

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0926

AC:

3843

AN:

41516

American (AMR)

AF:

0.366

AC:

5584

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1013

AN:

3472

East Asian (EAS)

AF:

0.310

AC:

1604

AN:

5178

South Asian (SAS)

AF:

0.301

AC:

1451

AN:

4826

European-Finnish (FIN)

AF:

0.345

AC:

3642

AN:

10554

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24114

AN:

67958

Other (OTH)

AF:

0.305

AC:

644

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1476

2951

4427

5902

7378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.330

Hom.:

38764

Bravo

AF:

0.275

Asia WGS

AF:

0.295

AC:

1028

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.6

(source)

DANN

Benign

0.40

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over